1. Field of the Invention
The present invention is directed to novel 6- or 7- (2-imino-2-imidazolidine)-1,4-benzoxazines which are active as alpha adrenergic agents, and particularly which are useful for treatment of glaucoma, renal and gastrointestinal disorders, vasoconstrictors and other diseases and conditions mediated by alpha-1 and alpha-2 receptors. In another aspect, the present invention is directed to pharmaceutical formulations or compositions which incorporate the novel compounds of the invention. In still another aspect, the present invention is directed to administering such formulations and compositions for the purpose of reducing or maintaining intraocular pressure (anti-glaucoma) and as vasoconstrictors, for example for controlling ocular bleeding, in mammalian species, including humans.
2. Brief Description of the Prior Art
Alpha adrenergic agents are known in the art. Whereas alpha-1 agonists are known to include compounds which have vasoconstrictor activity and are thus useful for controlling intraocular bleeding, alpha-2 agonist are known to include compounds useful for reducing intraocular pressure (anti-glaucoma effect), for increasing renal flow (diuretics) and for altering the rate of fluid transport in the gastrointestinal tract (anti-diarrheals).
In an article titled "Heteroaromatic Analogues of the alpha.sub.2 -Adrenoreceptor Partial Agonist Clonidine" J. Med. Chem. 1989, 32, 1627-1630, Chapleo et al. describe 6-(2-iminoimidazolidine)-3-oxo-3,4-dihydro-(2H)-1,4-benzoxazine and 7-(2-imino-imidazlidine)-3-oxo-3,4-dihydro-(2H)-1,4-benzoxazi compounds as partial alpha-2 agonists.
U.S. Pat. No. 3,890,319 discloses (2-imidazolin-2-ylamino- substituted quinoxalines as regulators of the cardiovascular system.
U.S. Pat. No. 4,515,800, describes 2-(trisubstituted phenylimino)imidazoline compounds [also known as 2-(trisubstituted-anilino)-1,3-diazacyclopentene-(2) compounds] in pharmaceutical compositions, preferably in eye drops, for the treatment of glaucoma.
U.S. Pat. No. 4,587,257 discloses 2-(trisubstituted phenylimino)imidazoline compounds capable of controlling ocular bleeding;
U.S. Pat. No. 3,636,219 discloses 2-(substituted-phenylamino)-thiazolines and imidazolines having anticholinergic activity.